The host metabolite D-serine contributes to bacterial niche specificity through gene selection

Escherichia coli comprise a diverse array of both commensals and niche-specific pathotypes. The ability to cause disease results from both carriage of specific virulence factors and regulatory control of these via environmental stimuli. Moreover, host metabolites further refine the response of bacteria to their environment and can dramatically affect the outcome of the host–pathogen interaction. Here, we demonstrate that the host metabolite, D-serine, selectively affects gene expression in E. coli O157:H7. Transcriptomic profiling showed exposure to D-serine results in activation of the SOS response and suppresses expression of the Type 3 Secretion System (T3SS) used to attach to host cells. We also show that concurrent carriage of both the D-serine tolerance locus (dsdCXA) and the locus of enterocyte effacement pathogenicity island encoding a T3SS is extremely rare, a genotype that we attribute to an ‘evolutionary incompatibility’ between the two loci. This study demonstrates the importance of co-operation between both core and pathogenic genetic elements in defining niche specificity

Repeat-sequence turnover shifts fundamentally in species with large genomes

Given the 2,400-fold range of genome sizes (0.06–148.9 Gbp (gigabase pair)) of seed plants (angiosperms and gymnosperms) with a broadly similar gene content (amounting to approximately 0.03 Gbp), the repeat-sequence content of the genome might be expected to increase with genome size, resulting in the largest genomes consisting almost entirely of repetitive sequences. Here we test this prediction, using the same bioinformatic approach for 101 species to ensure consistency in what constitutes a repeat. We reveal a fundamental change in repeat turnover in genomes above around 10 Gbp, such that species with the largest genomes are only about 55% repetitive. Given that genome size influences many plant traits, habits and life strategies, this fundamental shift in repeat dynamics is likely to affect the evolutionary trajectory of species lineages.We thank Natural Environment Research Council (NE/G020256/1), the Czech Academy of Sciences (RVO:60077344) and Ramón y Cajal Fellowship (RYC-2017-2274) funded by the Ministerio de Ciencia y Tecnología (Gobierno de España) for support. We also thank Natural Environment Research Council for funding a studentship to S.D. and the China Scholarship Council for funding W.W.Abstract Main Methods Data availability Code availability References Acknowledgements Author information Ethics declarations Additional information Extended data Supplementary information Rights and permissions About this article Further readin

Extant diversity of bryophytes emerged from successive post-Mesozoic diversification bursts

Unraveling the macroevolutionary history of bryophytes, which arose soon after the origin of land plants but exhibit substantially lower species richness than the more recently derived angiosperms, has been challenged by the scarce fossil record. Here we demonstrate that overall estimates of net species diversification are approximately half those reported in ferns and similar to 30% those described for angiosperms. Nevertheless, statistical rate analyses on time-calibrated large-scale phylogenies reveal that mosses and liverworts underwent bursts of diversification since the mid-Mesozoic. The diversification rates further increase in specific lineages towards the Cenozoic to reach, in the most recently derived lineages, values that are comparable to those reported in angiosperms. This suggests that low diversification rates do not fully account for current patterns of bryophyte species richness, and we hypothesize that, as in gymnosperms, the low extant bryophyte species richness also results from massive extinctions.Assembling the Tree of Life programme at NSF; NSF [EF-0531730-002, EF-0531680, EF-0531750]; Scottish Government's Rural and Environment Science and Analytical Services Division; BeiPD-cofund Marie Curie fellowshipinfo:eu-repo/semantics/publishedVersio

Population structure and genetic history of Tibetan Terriers

International audienceAbstractBackgroundTibetan Terrier is a popular medium-sized companion dog breed. According to the history of the breed, the western population of Tibetan Terriers includes two lineages, Lamleh and Luneville. These two lineages derive from a small number of founder animals from the native Tibetan Terrier population, which were brought to Europe in the 1920s. For almost a century, the western population of Tibetan Terriers and the native population in Tibet were reproductively isolated. In this study, we analysed the structure of the western population of Tibetan Terriers, the original native population from Tibet and of different crosses between these two populations. We also examined the genetic relationships of Tibetan Terriers with other dog breeds, especially terriers and some Asian breeds, and the within-breed structure of both Tibetan Terrier populations.ResultsOur analyses were based on high-density single nucleotide polymorphism (SNP) array (Illumina HD Canine 170 K) and microsatellite (18 loci) genotypes of 64 Tibetan Terriers belonging to different populations and lineages. For the comparative analysis, we used 348 publicly available SNP array genotypes of dogs from other breeds. We found that the western population of Tibetan Terriers and the native Tibetan Terriers clustered together with other Asian dog breeds, whereas all other terrier breeds were grouped into a separate group. We were also able to differentiate the western Tibetan Terrier lineages (Lamleh and Luneville) from the native Tibetan Terrier population.ConclusionsOur results reveal the relationships between the western and native populations of Tibetan Terriers and support the hypothesis that Tibetan Terrier belongs to the group of ancient dog breeds of Asian origin, which are close to the ancestors of the modern dog that were involved in the early domestication process. Thus, we were able to reject the initial hypothesis that Tibetan Terriers belong to the group of terrier breeds. The existence of this native population of Tibetan Terriers at its original location represents an exceptional and valuable genetic resource

Drug-eluting stents appear superior to bare metal stents for vein-graft PCI in vessels up to a stent diameter of 4 mm.

BACKGROUND: Research trials have shown improved short-term outcome with drug-eluting stents (DES) over bare metal stents (BMS) in saphenous vein graft (SVG) percutaneous coronary intervention (PCI), primarily by reducing target vessel revascularization (TVR) for in-stent restenosis. We compared the outcomes in patients undergoing SVG stent implantation treated with DES or BMS. In exploratory analyses we investigated the influence of stent generation and diameter. METHODS: Data were obtained from a prospective database of 657 patients who underwent PCI for SVG lesions between 2003 and 2011. A total of 344 patients had PCI with BMS and 313 with DES. Propensity scores were developed based on 15 observed baseline covariates in a logistic regression model with stent type as the dependent variable. The nearest-neighbour-matching algorithm with Greedy 5-1 Digit Matching was used to produce two patient cohorts of 313 patients each. We assessed major adverse cardiac events (MACE) out to a median of 3.3 years (interquartile range: 2.1-4.1). MACE was defined as all-cause mortality, myocardial infarction (MI), TVR and stroke. RESULTS: There was a significant difference in MACE between the two groups in favour of DES (17.9% DES vs. 31.2% BMS group; p = 0.0017) over the 5-year follow-up period. MACE was driven by increased TVR in the BMS group. There was no difference in death, MI or stroke. Adjusted Cox analysis confirmed a decreased risk of MACE for DES compared with BMS 0.75 (95% confidence interval (CI) 0.52-0.94), with no difference in the hazard of all-cause mortality (hazard ratio: 1.08; 95% CI: 0.77-1.68). However, when looking at stent diameters greater than 4 mm, no difference was seen in MACE rates between BMS and DES. CONCLUSIONS: Overall in our cohort of patients who had PCI for SVG disease, DES use resulted in lower MACE rates compared with BMS over a 5-year follow-up period; however, for stent diameters over 4 mm no difference in MACE rates was seen

Characterization of Modular Bacteriophage Endolysins from Myoviridae Phages OBP, 201ϕ2-1 and PVP-SE1

Peptidoglycan lytic enzymes (endolysins) induce bacterial host cell lysis in the late phase of the lytic bacteriophage replication cycle. Endolysins OBPgp279 (from Pseudomonas fluorescens phage OBP), PVP-SE1gp146 (Salmonella enterica serovar Enteritidis phage PVP-SE1) and 201ϕ2-1gp229 (Pseudomonas chlororaphis phage 201ϕ2-1) all possess a modular structure with an N-terminal cell wall binding domain and a C-terminal catalytic domain, a unique property for endolysins with a Gram-negative background. All three modular endolysins showed strong muralytic activity on the peptidoglycan of a broad range of Gram-negative bacteria, partly due to the presence of the cell wall binding domain. In the case of PVP-SE1gp146, this domain shows a binding affinity for Salmonella peptidoglycan that falls within the range of typical cell adhesion molecules (Kaff = 1.26×106 M−1). Remarkably, PVP-SE1gp146 turns out to be thermoresistant up to temperatures of 90°C, making it a potential candidate as antibacterial component in hurdle technology for food preservation. OBPgp279, on the other hand, is suggested to intrinsically destabilize the outer membrane of Pseudomonas species, thereby gaining access to their peptidoglycan and exerts an antibacterial activity of 1 logarithmic unit reduction. Addition of 0.5 mM EDTA significantly increases the antibacterial activity of the three modular endolysins up to 2–3 logarithmic units reduction. This research work offers perspectives towards elucidation of the structural differences explaining the unique biochemical and antibacterial properties of OBPgp279, PVP-SE1gp146 and 201ϕ2-1gp229. Furthermore, these endolysins extensively enlarge the pool of potential antibacterial compounds used against multi-drug resistant Gram-negative bacterial infections

All You Can Eat: High Performance Capacity and Plasticity in the Common Big-Eared Bat, Micronycteris microtis (Chiroptera: Phyllostomidae)

Ecological specialization and resource partitioning are expected to be particularly high in the species-rich communities of tropical vertebrates, yet many species have broader ecological niches than expected. In Neotropical ecosystems, Neotropical leaf-nosed bats (Phyllostomidae) are one of the most ecologically and functionally diverse vertebrate clades. Resource partitioning in phyllostomids might be achieved through differences in the ability to find and process food. We selected Micronycteris microtis, a very small (5–7 g) animalivorous phyllostomid, to explore whether broad resource use is associated with specific morphological, behavioral and performance traits within the phyllostomid radiation. We documented processing of natural prey and measured bite force in free-ranging M. microtis and other sympatric phyllostomids. We found that M. microtis had a remarkably broad diet for prey size and hardness. For the first time, we also report the consumption of vertebrates (lizards), which makes M. microtis the smallest carnivorous bat reported to date. Compared to other phyllostomids, M. microtis had the highest bite force for its size and cranial shape and high performance plasticity. Bite force and cranial shape appear to have evolved rapidly in the M. microtis lineage. High performance capacity and high efficiency in finding motionless prey might be key traits that allow M. microtis, and perhaps other species, to successfully co-exist with other gleaning bats

A Quasi-Exclusive European Ancestry in the Senepol Tropical Cattle Breed Highlights the Importance of the slick Locus in Tropical Adaptation

Background: The Senepol cattle breed (SEN) was created in the early XXth century from a presumed cross between a European (EUT) breed (Red Poll) and a West African taurine (AFT) breed (N'Dama). Well adapted to tropical conditions, it is also believed trypanotolerant according to its putative AFT ancestry. However, such origins needed to be verified to define relevant husbandry practices and the genetic background underlying such adaptation needed to be characterized. Methodology/Principal Findings: We genotyped 153 SEN individuals on 47,365 SNPs and combined the resulting data with those available on 18 other populations representative of EUT, AFT and Zebu (ZEB) cattle. We found on average 89% EUT, 10.4% ZEB and 0.6% AFT ancestries in the SEN genome. We further looked for footprints of recent selection using standard tests based on the extent of haplotype homozygosity. We underlined i) three footprints on chromosome (BTA) 01, two of which are within or close to the polled locus underlying the absence of horns and ii) one footprint on BTA20 within the slick hair coat locus, involved in thermotolerance. Annotation of these regions allowed us to propose three candidate genes to explain the observed signals (TIAM1, GRIK1 and RAI14). Conclusions/Significance: Our results do not support the accepted concept about the AFT origin of SEN breed. Initial AFT ancestry (if any) might have been counter-selected in early generations due to breeding objectives oriented in particular toward meat production and hornless phenotype. Therefore, SEN animals are likely susceptible to African trypanosomes which questions the importation of SEN within the West African tsetse belt, as promoted by some breeding societies. Besides, our results revealed that SEN breed is predominantly a EUT breed well adapted to tropical conditions and confirmed the importance in thermotolerance of the slick locus. (Résumé d'auteur

Chronic hepatitis c genotype-4 infection: role of insulin resistance in hepatocellular carcinoma

<p>Abstract</p> <p>Background</p> <p>Hepatitis C virus (HCV) is a major cause of chronic hepatitis and hepatocellular carcinoma (HCC) and different HCV genotypes show characteristic variations in their pathological properties. Insulin resistance (IR) occurs early in HCV infection and may synergize with viral hepatitis in HCC development. Egypt has the highest reported rates of HCV infection (predominantly genotype 4) in the world; this study investigated effects of HCV genotype-4 (HCV-4) on prevalence of insulin resistance in chronic hepatitis C (CHC) and HCC in Egyptian patients.</p> <p>Methods</p> <p>Fifty CHC patients, 50 HCC patients and 20 normal subjects were studied. IR was estimated using HOMA-IR index and HCV-4 load determined using real-time polymerase chain reaction. Hepatitis B virus was excluded by enzyme-linked immunosorbent assay. Standard laboratory and histopathological investigations were undertaken to characterize liver function and for grading and staging of CHC; HCC staging was undertaken using intraoperative samples.</p> <p>Results</p> <p>HCC patients showed higher IR frequency but without significant difference from CHC (52% vs 40%, p = 0.23). Multivariate logistic regression analysis showed HOMA-IR index and International Normalization Ratio independently associated with fibrosis in CHC; in HCC, HbA1c, cholesterol and bilirubin were independently associated with fibrosis. Fasting insulin and cholesterol levels were independently associated with obesity in both CHC and HCC groups. Moderate and high viral load was associated with high HOMA-IR in CHC and HCC (p < 0.001).</p> <p>Conclusions</p> <p>IR is induced by HCV-4 irrespective of severity of liver disease. IR starts early in infection and facilitates progression of hepatic fibrosis and HCC development.</p

Role of Hepatic Lipase and Endothelial Lipase in High-Density Lipoprotein—Mediated Reverse Cholesterol Transport

Reverse cholesterol transport (RCT) constitutes a key part of the atheroprotective properties of high-density lipoproteins (HDL). Hepatic lipase (HL) and endothelial lipase (EL) are negative regulators of plasma HDL cholesterol levels. Although overexpression of EL decreases overall macrophage-to-feces RCT, knockout of both HL and EL leaves RCT essentially unaffected. With respect to important individual steps of RCT, current data on the role of EL and HL in cholesterol efflux are not conclusive. Both enzymes increase hepatic selective cholesterol uptake; however, this does not translate into altered biliary cholesterol secretion, which is regarded the final step of RCT. Also, the impact of HL and EL on atherosclerosis is not clear cut; rather it depends on respective experimental conditions and chosen models. More mechanistic insights into the diverse biological properties of these enzymes are therefore required to firmly establish EL and HL as targets for the treatment of atherosclerotic cardiovascular disease